Nexavar, vitamin K increase progression-free survival of HCC

SAN FRANCISCO — Vitamin K administered to patients at the time of treatment with Nexavar for hepatocellular carcinoma increased overall and progression-free survival, according to data presented at The Liver Meeting 2015.

Researchers from Osaka General Medical Center, Japan, evaluated 55 patients with HCC who underwent treatment with 45 mg of vitamin K2 along with Nexavar (sorafenib, Bayer HealthCare; n = 20) or treatment with sorafenib alone.

“We examined retrospectively for HCC, focusing on changes of serum des-γ-carboxy prothrombin (DCP) levels (pretreatment vs. 8 weeks after the start of treatment),” Yoshimichi Haruna MD, PhD, department of gastroenterology and hepatology, Osaka General Medical Center, Osaka, Japan, said during his presentation. “There were no relevant differences between the vitamin K combination and sorafenib alone groups in characteristics at baseline.”

Overall, the researchers found a significant difference in progression-free survival time between the two groups, according to Haruna.

“The median profession-free survival was 8 months in the vitamin K group vs. 2.5 months in the sorafenib alone group (P < .001),” Haruna said.

The disease control rate was higher in the vitamin K and sorafenib group (78.9%) compared with the sorafenib alone group (22.9%; P < .001). In addition, patients treated with vitamin K had prolonged overall survival compared with patients treated with sorafenib alone (23 vs. 10 months; P = .002).

Serum DCP levels increased in the sorafenib alone group (2.42 ± 0.92 to 2.78 ± 0.95 log mAU/mL; P = .051) despite suppressed tumor growth. However, patients in the vitamin K-treated group had significant decline in serum DCP (2.35 ± 0.56 to 1.38 ± 0.2 log mAU/mL; P = .001).

“Our speculation for these findings is the following: Sorafenib deteriorates tumor angiogenesis and put tumor cells in ischemic status, which impairs vitamin K uptake of tumor cells to increase DCP production. DCP is believed to work for tumor and endothelial cells as a growth factor. The large scale of vitamin K dosing decreases DCP production by increased vitamin K concentration inside tumor cells. Thus, vitamin K dosing may enhance sorafenib’s antitumor action by suppressed DCP levels,” Haruna told Healio.com/Hepatology.

Haruna concluded in his presentation: “The nontoxic agent, vitamin K, dosing during sorafenib treatment for HCC markedly prolonged OS as well as [progression-free survival] probably by augmented ischemic damage of tumor cells.” – by Melinda Stevens

Reference:

Haruna Y, et al. Abstract 173. Presented at: The Liver Meeting; Nov. 13-17, 2015; San Francisco.

Disclosures: The researchers report no relevant financial disclosures.

Editor's note: This article has been updated with an additional quote from the presenter.